Wilson’s Disease

By Dr Husnain Irshad Alvi

Resident Physician of
Internal Medicine (MU-3)
INTRODUCTION

• Wilson’s Disease (Hepatolenticular Degeneration) is a rare disease

and its an Autosomal Recessive Disorder of Copper metabolism.
• It occurs due to mutation in ATP7B gene on Cr: 13.
• Remember ATP7A gene mutation causes Menkes Disease.
• Mutation causes Increase amount of Total body copper which is
deposited on Organs leading to damage.
• Organs effected are Basal ganglia of Brain , Liver , Bone, Kidneys
and Cornea.
• Incidence of W.D is 1/30000 to 1/100000.
• Over 200 types of Mutations are discovered.
PATHOPHYSIOLOGY

• Normally Copper is reabsorbed from Stomach and Upper Smal Intestine.

• From there it is taken to liver loosely bound to Albumin.
•
• In Liver it binds with Ceruloplasmin and transported in Blood.

• Excess amount of copper is excreted in Bile and Feces.

• In Wilson disease decreased production of Ceruloplasmin is the reason for increased

amount of Serum free copper.
• Although 5% of people with Wilson disease have normal ceruloplasmin (reference
Davidson 23rd Ed).
CLINICAL FEATURES

• Liver Disease:- Mostly occurrs in children. It ranges from Acute Liver Failure
to Chronic to Cirrhosis.

• Neurological Disease:- Mostly Occurs in Adults and is characterized by

Extrapyramidal Symptoms like Choreoathetosis,Dysarthria, Tremors, Parkinson
Like Symptoms,Vecuous Smile,Dementia.
• Neurological Wilson is almost always associated with Kayser Fliescher Rings. It
is Copper deposition in descemet membrane of cornea visualise like Greenish
Brown Pigmentation ay Corneoscleral junction on Slit Lamp Examination.
Disappeare on Treatment.
• 4 stages of Wilson’s Disease.
CLINICAL FEATURES
 Kayser Fliescher Rings

Deposition starts from 6 and 12th position.Then spread

around whole cornea. Not necessarily a Pathognomonic
of Wilson’s as seen in PBC, Cryptogenic,Cr Active
Cirrhosis as well.
Vecuous Smile
 INVESTIGATIONS
• Serum Ceruloplasmin level (Best Single indicator Ref: Davidson).
Its level decreases in Wilson disease. But in 5% of cases it can be normal.
24 Hour Urine copper excretion is increased (100-1000 ug) Normal is <40 ug.
• Liver Biopsy shows Increase deposition of Copper (250 ug/g dry weight).
• Hemolysis and Anemia (Coomb Negative)
• Genetic Analysis is limited but done in selected population group (Ref: Perveen Kumar
Clinical Medicine)
• MRI brain for B.G ,Brain stem and cerebellar copper deposition.
Diagnosing Wilson’s is based on Leipzig Criteria (Decrease Serum Ceruloplasmin, Increase
24hr Urinary copper, Increase Hepatic Copper, KF ring , Coomb Negative Anemia,
Neurological symptoms).
• When Serum Ceruloplasmin is Normal then a rise in 24hr urine copper on Penicillamine
challenge test is Used in children.(lacks sensitivity so rarely used) (Reference CMDT
2021).
Treatment

• Treatment of Wilson’s Disease is For Lifetime.

• Treatment is divided into three steps.
1. Dietary Restrictions

2. Pharmacological treatment

3. Surgical Treatment
 Treatment
• Decreasing Dietary Intake of Copper containing foods like Chocolates and Peanuts ,
etc.
• Pharmacological Treatment :
1. D-Penicillamine (Copper binding Drug) is Drug of Choice ( 0.75-2gm/day in divided
doses). Add Pyridoxine 50mg /week as D-penicillamine is its antimetabolite.
• It acts by chelating copper and increasing removal of Copper from body. Have to
repeat urinary copper excretion after 2-3 years in order to lower down the dose of
Penicillamine.
Abrupt discontinuation can lead to Acute Liver Failure.
• Side effects are Rash, protein loosing enteropathy, Lupus like symptoms, Bone
marrow Suppression (Leucopenia), Nephrotoxicity.
2. Trentine Dihydrochloride (250-500mg TDS) act as D-penicillamine or oral Zinc
(50mg TDS) acts by decreasing Copper absorption in gut and increasing excretion in
feces in patients who developed S/E of Penicillamine or Asymptomatic or in
Pregnancy.
TREATMENT (cont.) , PROGNOSIS.

3. Ammonium Tetrathiomolybdate (complexes iron in Intestine) and

Bis-choline Tetrathiomolybdate are used as first line for Neurological
wilson and shown effective results.
• Surgical Treatment: Liver Transplantation in Acute Liver Failure or
Cirrhosis.
• Patient’s family members should be screened for ATP7B gene and
even if asymptomatic start Zinc therapy. (Ref Parveen Kumar).
• Excellent prognosis with Promt treatment without any irreversible
damage to liver or ALF or Brain damage by excess copper deposition.
SCENARIOS

• Q1. A 20 year old boy presented to your clinic with complain of Yellowish discoloration of eyes
and itching in body . On Examination Vitally Patient was stable. On Subvitals Only Juandice
and Pedal edema were positive finding.
Abdomen Palpation Liver not palpable and Spleen was 4 cm below left costal margin.
Serum Ceruloplasmin level was decreased with 24 Hour Urinary Copper of 600ug (Normal <40ug).
You advised Opthalmologist opinion for KF rings but were negative.
What is the Treatment you will advised to this patient?
A. Dietary restrictions and D-penicillamine plus Pyridoxine
B. Trentine Dihydrochloride (500mg Tds)
C. Liver transplantation
D. Zinc (50mg OD)
SCENARIOS

• Q2. A 35 year old writer presented to you with complain of abnormal jerky movements in hands
with tremors. Patient also complains drooling of saliva. On General Physical Examination you
observed patient have mask like face. Vitally stable . Patient had a episode of hematamesis 2
days back. Abdomen Examination liver was 16 cm in size. KF Rings positive on Slit lamp
Examination. You started D-penicillamine but after 15 days patient was brought to your ward
with no any movement and unable to speek or feed. You passed NG tube and changed your
treatment to Trentine Dihydrochloride. LFTs which were worse initially now showed
improvement but patient’s Neurological condition got worsened and now patient’s GCS is 7/15.
• Which Treatment option should be choosed now?
• A. Liver transplantation
• B.Zinc sulfate 50mg OD
• C.Ammonium Tetrathiomolybdate
• D.Continue Treatment with Trentine and D-penicillamine for indefinite period of time.
CONCLUSION

Consider Wilson in every patient age <40yr with Hepatitis

,Spleenomegaly , Portal HTN, Neurological symptoms and Hemolytic
anemia (coomb –ve).
• Wilson’s Parkinson have more better prognosis with early
treatment then idiopathic Parkinson in young.

THANK YOU